Cancer treatment communications最新文献

Thymomas are tumors arising from thymic epithelial cells that are frequently associated with autoimmune conditions. One such disorder, autoimmune enteropathy, is an uncommon autoimmune process found in patients with thymoma that is characterized by chronic diarrhea (>6 weeks duration), malabsorption, and characteristic small intestinal histopathology. The presence of anti-enterocyte or anti-goblet cell antibodies supports the diagnosis of autoimmune. As this is a relatively uncommon disorder, treatment options have not been well studied. We report the case of a 35-year-old Caucasian male with recurrent thymoma that subsequently developed autoimmune enteropathy as confirmed by symptoms, biopsy and serologies. Prednisone and octreotide, which have previously been shown to treat recurrent thymoma, were used to successfully treat his autoimmune enteropathy and recurrent thymoma, leading to resolution of diarrhea, subsequent weight gain, and radiographic confirmation of regression of metastatic thymoma. Autoimmune enteropathy should be considered in the differential diagnosis of patients with thymoma presenting with intractable diarrhea and weight loss. The use of prednisone and octreotide may be helpful in treating both conditions.

Recently, the state of oligometastases has been spotlighted in the treatment strategy for metastases. Aggressive local treatment for oligometastases, including pulmonary resection, stereotactic body radiotherapy (SBRT), radiofrequency ablation, and cryoablation has been the subject of research. Among studies on the local treatment, those on SBRT more often evaluated local control as the primary outcome, and those on pulmonary metastasectomy more often evaluated overall survival as the primary outcome. Oligometastases is a disease concept that is defined by a state of limited systemic metastatic tumors for which local ablative therapy could be curative. By definition, the purpose of local treatment for oligometastases is cure, and the primary outcome to be analyzed should be disease-free survival. As systemic adjuvant therapy in addition to local treatment with complete ablation has some effect on micrometastases, in clinical research on oligometastases, the only treatment modality under evaluation should be local ablation. There are multiple discrete indications for the local treatment of metastatic lesions. The purposes of these indications are (a) the intent to cure oligometastases, (b) the intent to prolong survival as a part of multidisciplinary therapy, and (c) local control for palliative care. In order to appropriately evaluate the significance of local treatment, the outcomes should depend on the indication for treatment. The corresponding outcomes to consider are (a) disease-free survival, (b) overall survival, and (c) local control. Factorial analysis of each outcome corresponding to each indication for local therapy would yield information on each clinical presentation to help decide treatment.

Introduction

The neutrophil–lymphocyte ratio (NLR) is prognostic in a number of tumour types, with conflicting results in metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to assess whether the NLR prior to the administration of premedication steroids is a prognostic marker in men with mCRPC treated with taxane-based chemotherapy.

Patients and methods

This was a retrospective study of men with mCRPC receiving taxane-based chemotherapy between 2005 and 2012. Patients were included if laboratory results were available between two and 28 days prior to the commencement of chemotherapy. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards regression models were used to determine the prognostic significance of NLR on OS and PFS.

Results

OS was significantly better in patients with NLR <5 (n=28) compared to those with NLR >5 (n=14), with median OS 32 months vs 14.9 months respectively (HR 2.15, 95% CI 1.07–4.33, p=0.0003). PFS was 10 months in those with NLR <5 vs 5 months in those with NLR >5 (HR 2, 95% CI 0.99–3.66, p=0.01). Multivariate analysis confirmed NLR (p=0.004) to be an independent prognostic factor for OS.

Conclusion

The findings from this study support the use of baseline NLR as a prognostic biomarker in men with mCRPC receiving taxane based chemotherapy. An elevated NLR (>5) is associated with a shorter survival in this group of patients.

A 14-year-old boy was referred to our hospital with a 1-year evolving productive cough and hemoptysis.A Positron-emission-tomography scan (PET/CT) revealed a 17cm hypermetabolic right lower-lobe lung mass in contact with mediastinal structures as well as multiple bilateral pulmonary nodules. Percutaneous lung biopsy identified an invasive mucinous adenocarcinoma (IMA; formerly mucinous BAC) associated with Type I Congenital Cystic Adenomatoid Malformation (CCAM).Genomic profiling was performed and detected a KRAS mutation (G12D).

NSCLC can be rarely seen in young patients. In the pediatric population, the incidence is approximately 0.0002% and it is usually associated with a congenital malformation.

CCAM is a group of rare lung congenital malformations. The estimated incidence is 1 in 25.000 to 1 in 35.000 pregnancies and it represents 25% of all congenital lung malformations. Type I is the most common subtype of CCAM. It is characterized by the presence of large cysts lined by pseudostratified ciliated cells that are often interspersed with rows of mucous cells.It has been largely recognized that some cases of type I CCAM show malignant transformation to mucinous adenocarcinoma.

Recent data clearly demonstrated that the occurrence of mucinous adenocarcinoma in type I CCAM is associated with KRAS mutation.

This case highlights the relationship between type I CCAM and lung mucinous adenocarcinoma/KRAS mutant. Moreover, demonstrated that the clinical outcome was consistent with the molecular feature of a KRAS mutant patient.

Objective

Heterogeneity of EGFR mutations remains controversial. A case of completely resected lung adenocarcinoma after initial chemotherapy with gefitinib that showed intratumoral heterogeneity of EGFR mutations is reported.

Patient and methods

A 68-year-old woman who presented with mild breathlessness was diagnosed with lung adenocarcinoma (cT3N1M0 stage IIIA) harboring the L858R point mutation. She received gefitinib as neo-adjuvant chemotherapy to reduce the tumor volume to avoid pneumonectomy, and she underwent right middle and lower lobectomies. The resected specimen showed two areas that were distinctly different pathologically and genetically within the tumor. One area consisted of viable cells, but the other consisted mostly of degenerated cells. Immunohistochemical staining and polymerase chain reaction-direct sequencing for each microdissected area were performed.

Results

In the viable cells area, the L858R point mutation was detected by both methods, but it was not detected in the mostly degenerated cells area.

Conclusion

These results suggest that there may be intratumoral heterogeneity of EGFR mutations, and the therapeutic effect of EGFR–TKIs could be limited only to mutant cells.

Neuroendocrine neoplasms (NENs) of the lung comprise a heterogeneous group, including small cell lung cancer (SCLC), large cell neuroendocrine carcinoma and pulmonary carcinoids. To unravel their molecular biology, microarray studies have been conducted that provided lists of differentially expressed genes between lung NENs on the one hand and normal tissue and/or non-SCLCs on the other. However, the majority of studies paid little attention to the functions of candidates and their potency as diagnostic markers and/or therapeutic targets. Furthermore, at a first glance, only limited overlap was seen amongst these individual studies concerning differentially expressed transcripts.

By combining all originally published gene expression profiling studies on lung NENs, and by re-evaluating differentially expressed genes, we were able to identify major factors involved in lung NEN carcinogenesis. Thirty-three genes were found to be frequently deregulated in multiple studies. Amongst these are neuroendocrine-specific factors, including ASH1, INSM1, and ISL1 and genes involved in neuronal differentiation and neurite outgrowth such as DCX and NCAM1. Also, multiple factors were involved in cell cycle progression, including members of the mitotic spindle checkpoint complex, and the regulated secretory pathway, e.g. CHGA and CHGB and CPE. For several of these candidates we propose possible functions in lung NEN carcinogenesis as well as potential roles in diagnosis and as targets for novel therapies.

This review elucidates potential genes of interest in pulmonary NENs on basis of the present expression profiling literature. We advocate that a selection of the identified candidates should be examined in depth for their clinical application.

The Surveillance, Epidemiology, and End Results (SEER 18) database is the largest national registry for cancer-related patient data in the United States. Black populations consistently have shown poorer survival statistics, possibly due to later stages of presentation, increased tumor aggressiveness, treatment noncompliance, or other debated causes. Our goal in this study is to look at a socioeconomic marker that may link all of these causes, namely median income level, and derive the extent of influence a patient's financial resources can have on overall survival. Original cases from the aforementioned database were identified, with unknown racial status cases excluded from the final dataset. Survival data by geographical county was collected from the SEER database and correlated to US Census Bureau median income data to uncover meaningful statistical relationships. Blacks were noted to present at later ages (60+years), with deeper invasive lesions (median 1.255 mm vs 0.60 mm), and higher rates of ulceration (35.9% vs 13.0%) than White patients. Whites were found to overall fare better than Blacks for all time intervals (Year 1–5) following diagnosis, based on mean survival data (p<0.05). Blacks have higher survival rates for the same time intervals (Year 1 to Year 5) when survival statistics adjusted for income (p<0.05). Significant correlations were seen between presentation parameters, income, and overall survival. These findings identify a major socioeconomic issue to address within the policy-making framework and endorse earlier intervention for underprivileged populations.

New areas of research continue to examine the role of non-androgen receptor pathways in prostate cancer treatment. The phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway may be a target for prostate cancer therapy. Somatostatin receptor signaling inhibits intracellular PI3K/Akt signaling, making it an attractive target for combination therapy. We conducted a phase II open label clinical trial examining the use of somatostatin receptor agonist, pasireotide (SOM230) in combination with mTOR inhibitor, everolimus in metastatic castrate-resistant chemotherapy-naïve prostate cancer patients. Of the 6 patients enrolled in the study, only 1 patient had >50% PSA reduction from baseline. Three patients withdrew due to grade 3 adverse events. The study was closed early due to toxicity profiles and no further development was planned for this combination treatment in prostate cancer.

Background

Paraneoplastic leukemoid reaction (PLR) is a well-described entity in which the white blood cell count expands to greater than 50,000/mm³ in association with malignancy. It is thought to occur in approximately 10–15% of cancers. Notably, PLR is known to be predictive of a poor prognosis. Recent work has demonstrated that there may be a relationship between PLR activated by intratumoral production of granulocyte colony-simulating factor (G-CSF), the RAS/RAF/MEK pathway and tumorogenesis. Specifically, activation of the RAS/RAF/MEK pathway is thought to regulate G-CSF production, which in turn, mediates expansion and mobilization of cells that produce factors that promote tumor metastasis.

Methods/results

In this report we demonstrate the PLR response to treatment in a patient with non-small cell lung cancer. Additionally, we demonstrate elevated G-CSF in the patient׳s serum 507 pg/ml (0–39.1 pg/ml) and positive staining by immunohistochemistry of G-CSF in the patient׳s tumor tissue. Finally, we describe a possible pathway by which this promotes tumor spread.

Conclusion

Though G-CSF has been traditionally viewed as a prognostic marker, here we provide evidence that it may be a valuable marker to investigate for treatment response at a cellular level.

Purpose: as the use of accelerated partial breast irradiation (APBI) becomes more widely used it is important to define and characterize the possible toxicities encountered with this type of therapy to help understand how to prevent these toxicities in the future.

Methods and materials: a 60-year-old woman was treated with APBI using external beam radiation. Three weeks post radiation therapy, she was given a cycle of docetaxel and cyclophosphamide. Within 3 weeks of chemotherapy she developed a radiation dermatitis ulceration in her right axilla and tail of her right breast. Little data exists regarding the association between the actual volume of skin irradiated during external beam APBI and the development of skin toxicity such as RRD, therefore we analyzed the volume of skin getting various prescription doses in our patient and compared them to 30 similar breast cancer patients treated with external beam radiation APBI at the same institution.

Results: our patient׳s volume of skin getting 100%, 90% and 80% of the prescription dose was below the mean for all three doses when compared to all other patient׳s treated similarly at our institution.

Conclusions: we present an example of radiation recall dermatitis in a patient receiving APBI with external beam radiation followed by chemotherapy. In our case, volume of skin irradiated did not appear to be associated with the development of RRD, therefore other factors may have led to her development of this rare skin reaction.